The role of neurosteoids sulphate in a spatial and object recognition learning task

Abstract

The term “neuroactive steroid” refers to steroids that have rapid modulatory effects on ligand-gated ion channels via non-genomic mechanism. Specifically, neurosteroids can alter neuronal excitability via the cell surface interacting with specific neurotransmitter receptors. The neurosteroid pregnenolone sulphate (PREGS) has been described as negative modulator of GABAA receptor and positive modulator of NMDA receptor, affecting cognition as well as emotionality. The present study was aimed to assess the effects of the acute administration of PREGS (10 mg/Kg, s. c.) on rats cognitive functions using a novel task, the Can test. This task explores, under reinforcement, the spatial/visual cues of the rats, along four sequential experimental sessions: shaping, spatial acquisition, retention and simple visual task. Our results show that acute treatment with PREGS induced a significant improvement in spatial orientation acquisition and retention (p< 0.001; p< 0.01), and increased the natural exploratory activity of rodents in a simple visual task (p< 0.001)when compared to control. The learning and memory enhancing properties of PREGS seem to be due to the potentiation of the central cholinergic transmission, as shown by electrophysiological recordings in the CA3 hippocampal area and in the perirhinal cortex. These findings provide additional evidence that neuroactive steroids have memory-enhancing properties and may constitute potential therapeutic tools for the treatment of cognitive deficits